It has been demonstrated that pre-treatment of mouse lymphoid cells with anti-Ia (I-region-associated) sera and complement (C) abrogates the T-cell proliferative response to Con A and lentil lectin, but not PHA. Reconstitution experiments have shown that a glass adherent, non-T, non-B, 1000R resistant accessory cell is the target in the abrogation of the response to Con A by anti-Ia and C. Genetic studies have shown that the Ia determinants expressed on these accessory cells are encoded by at least two different subregions of the I-locus. These determinants appear to be expressed on the same cell. Treatment with anti-Ia sera and C has also been shown to prevent the generation of CML (cell-mediated lympholysis) suppressor cells induced by 5-day culturing of normal spleen cells. These Ia+ accessory cells have also been shown to be essential for the in vitro generation of Ir gene controlled as well as non-Ir gene controlled T-cell dependent IgM responses to soluble TNP-conjugated protein antigens.